Current understanding of the pathogenetic relationships between chronic obstructive pulmonary disease and type 2 diabetes mellitus: an integrative review

Authors

DOI:

https://doi.org/10.26641/2307-0404.2025.3.340743

Keywords:

chronic obstructive pulmonary disease, type 2 diabetes, obesity

Abstract

Currently, chronic obstructive pulmonary disease (COPD) is considered a systemic disease with multiple extrapulmonary effects, which is caused by systemic manifestations of the inflammatory process. On the other hand, obesity, oxidative stress, chronic hyperglycemia, and insulin resistance, inherent in type 2 diabetes mellitus (DM), are key factors for enhancing the body's inflammatory response. Our study aimed to review the existing scientific literature to determine the patterns, relationships, and pathogenetic relationships between type 2 diabetes mellitus and chronic obstructive pulmonary disease. The empirical research method of modern English-language medical literature was used in depth from 2003 to 2024, using search engines on the PubMed and Google Scholar platforms and the Scopus and Web of Science abstract scientific literature databases, and the Cochrane scientific library. Based on the search results, 59 information sources were selected and processed.The analysis used system-structural, formal-logical, bibliographic, and informal (traditional) methods. The authors designed their own figures to visually present information using the infographic methods based on the Miro web resource (miro.com). It has been shown that patients with type 2 diabetes mellitus have an increased risk of developing COPD due to active systemic inflammation, obesity, insulin resistance, and oxidative stress. In addition, hyperglycemia contributes to decreased lung functional parameters and airway remodeling. Adipose tissue plays a vital role in the pathogenesis of COPD and type 2 diabetes mellitus by producing adipokines, such as leptin, resistin, adiponectin, and omentin. An imbalance between pro- and anti-inflammatory adipokines contributes to chronic inflammation, leading to lung function deterioration. Oxidative stress caused by chronic hyperglycemia is an essential factor in the pathogenesis of COPD. Reactive oxygen species (ROS) activate signaling pathways that lead to chronic inflammation and damage to lung tissue. Chronic hyperglycemia affects the function of bronchial smooth muscles, causing its hyperreactivity and excessive proliferation, which can worsen the course of COPD. Thus, COPD and type 2 diabetes are closely interconnected at the level of pathogenetic mechanisms, and the presence of one of these diseases may contribute to the development and progression of the other. Further studies of these relationships may contribute to developing more effective approaches to diagnosing, treating, and prevention of given pathologies.

References

Celli B, Fabbri L, Criner G, et al. Definition and nomenclature of chronic obstructive pulmonary disease: time for its revision. Am J Resp Crit Care Med. 2022;206(11):1317-25. doi: https://doi.org/10.1164/rccm.202204-0671PP

Di Stefano A, Gnemmi I, Dossena F, Ricciar-dolo FL, Maniscalco M, Lo Bello F, et al. Pathogenesis of COPD at the cellular and molecular level. Minerva Medica. 2022 Jun;113(3):405-23. doi: https://doi.org/10.23736/S0026-4806.22.07927-7

MacNee W. ABC of chronic obstructive pulmo-nary disease. Pathology, pathogenesis, and pathophy-siology. BMJ. 2006;332:1202-4. doi: https://doi.org/10.1136/bmj.332.7551.1202

Lange P, Ahmed E, Lahmar ZM, Martinez FJ, Bourdin A. Natural history and mechanisms of COPD. Respirology. 2021;26:298-321. doi: https://doi.org/10.1111/resp.14007

Chen X-R, Wang D-X. Serum MCP-1 and NGAL are important in the acute inflammatory event of chronic obstructive pulmonary disease. COPD: Journal of Chronic Obstructive Pulmonary Disease. 2021;18:425-31. doi: https://doi.org/10.1080/15412555.2021.1954151

Barnes PJ. The cytokine network in asthma and chronic obstructive pulmonary disease. Journal of Clinical Investigation. 2008;118:3546-56. doi: https://doi.org/10.1172/jci36130

Cornwell W, Kim V, Song C, Rogers T. Patho-genesis of inflammation and repair in advanced COPD. Seminars in Respiratory and Critical Care Medicine. 2010;31:257-66.

doi: https://doi.org/10.1055/s-0030-1254066

Xu J, Zeng Q, Li S, Su Q, Fan H. Inflammation mechanism and research progress of COPD. Frontiers in Immunology. 2024 Aug 9;15:1404615. doi: https://doi.org/10.3389/fimmu.2024.1404615

Agustí AGN, Noguera A, Sauleda J, Sala E, Pons J, Busquets X. Systemic effects of chronic ob-structive pulmonary disease. European Respiratory Journal. 2003;21:347-60. doi: https://doi.org/10.1183/09031936.03.00405703

Khanna D, Khanna S, Khanna P, Kahar P, Patel BM. Obesity: a chronic low-grade inflammation and its markers. Cureus. 2022 Feb 28;14(2):e22711. doi: https://doi.org/10.7759/cureus.22711

González P, Lozano P, Ros G, Solano F. Hyperglycemia and oxidative stress: an integral, updated and critical overview of their metabolic interconnections. International Journal of Molecular Sciences. 2023;24(11):9352. doi: https://doi.org/10.3390/ijms24119352

Liu J, Han X, Zhang T, Tian K, Li Z, Luo F. Reactive oxygen species (ROS) scavenging biomaterials for anti-inflammatory diseases: from mechanism to therapy. Journal of Hematology & Oncology. 2023 Nov 30;16(1):116. doi: https://doi.org/10.1186/s13045-023-01512-7

Chandrasekaran P, Weiskirchen R. The role of obesity in type 2 diabetes mellitus – an overview. International Journal of Molecular Sciences. 2024;25:1882. doi: https://doi.org/10.3390/ijms25031882

Antomonov MY. [Mathematical processing and analysis of medical and biological data]. Kyiv; 2018. 579 p. Ukrainian.

Damania D, Hameed S, Eng A, Douen A, Khanijao S, Sajawal Q, et al. Role of diabetes in exacerbation of COPD. Chest. 2021;160:A1888. doi: https://doi.org/10.1016/j.chest.2021.07.1678

Su J, Li M, Wan X, Yu H, Wan Y, Hang D, et al. Associations of diabetes, prediabetes and diabetes duration with the risk of chronic obstructive pulmonary disease: a prospective UK Biobank study. Diabetes, Obesity and Metabolism. 2023;25:2575-85. doi: https://doi.org/10.1111/dom.15142

Chiu HT, Li TC, Li CI, Liu CS, Lin WY, Lin CC. Visit-to-visit glycemic variability is a strong predictor of chronic obstructive pulmonary disease in patients with type 2 diabetes mellitus: competing risk analysis using a national cohort from the Taiwan diabetes study. PLOS ONE. 2017;12:e0177184. doi: https://doi.org/10.1371/journal.pone.0177184

Chen G, Lin Q, Zhuo D, Cui J. Elevated blood glucose is associated with severe exacerbation of chronic obstructive pulmonary disease. International Journal of Chronic Obstructive Pulmonary Disease. 2022;17:2453-59. doi: https://doi.org/10.2147/copd.s378259

Agarwal A, Grover A, Agarwal A. Pulmonary function test in patients of type 2 diabetes mellitus. International Journal of Research in Medical Sciences. 2019;7:2240.

doi: https://doi.org/10.18203/2320-6012.ijrms20192505

Sharma A, Sharma A, Chauhan R. Spirometric lung functions in type 2 diabetes mellitus: a hospital-based study. Cureus. 2023 May 12;15(5):e38919. doi: https://doi.org/10.7759/cureus.38919

Vaishnav BT, Gangani SK, Anand S, Ruchitha P, Mondkar S. Comparative study of spirometry parameters in chronic smokers with and without type 2 diabetes mellitus (T2DM). Journal of Family Medicine and Primary Care. 2024;13:2921-26. doi: https://doi.org/10.4103/jfmpc.jfmpc_1770_23

Chernetska NV. [Features of the combined course of chronic obstructive pulmonary disease and type 2 diabetes mellitus]. Klinichna ta eksperymentalna patolohiia. 2020;19:138-43. doi: https://doi.org/10.24061/1727-4338. XІX.3.73.2020.19

Clemente-Suárez VJ, Redondo-Flórez L, Beltrán-Velasco AI, Martín-Rodríguez A, Martínez-Guardado I, Navarro-Jiménez E, et al. The role of adipokines in health and disease. Biomedicines. 2023;11:1290. doi: https://doi.org/10.3390/biomedicines11051290

Taylor EB. The complex role of adipokines in obesity, inflammation, and autoimmunity. Clinical Science. 2021;135(6):731-52. doi: https://doi.org/10.1042/CS20200895

Zhang J, Lu E, Deng L, Zhu Y, Lu X, Li X, et al. Immunological roles for resistin and related adipokines in obesity-associated tumors. International Immunopharma¬cology. 2024;142:112911. doi: https://doi.org/10.1016/j.intimp.2024.112911

Iacobazzi D, Convertini P, Todisco S, Santar-siero A, Iacobazzi V, Infantino V. New insights into NF-κB signaling in innate immunity: focus on immuno-metabolic crosstalks. Biology. 2023;12:776. doi: https://doi.org/10.3390/biology12060776

Choi HM, Doss HM, Kim KS. Multifaceted physiological roles of adiponectin in inflammation and diseases. International Journal of Molecular Sciences. 2020;21:1219. doi: https://doi.org/10.3390/ijms21041219

Ramos-Ramírez P, Malmhäll C, Tliba O, Rådin-ger M, Bossios A. Adiponectin/AdipoR1 axis promotes IL-10 release by human regulatory T cells. Frontiers in Immunology. 2021 May 18;12:677550. doi: https://doi.org/10.3389/fimmu.2021.677550

Salvator H, Grassin-Delyle S, Brollo M, Couderc L-J, Abrial C, Victoni T, et al. Adiponectin inhibits the production of TNF-α, IL-6 and chemokines by human lung macrophages. Frontiers in Pharmacology. 2021;12:718929. doi: https://doi.org/10.3389/fphar.2021.718929

Sena CM. Omentin: a key player in glucose homeostasis, atheroprotection, and anti-inflammatory potential for cardiovascular health in obesity and diabetes. Biomedicines. 2024;12:284. doi: https://doi.org/10.3390/biomedicines12020284

Kocot J, Dziemidok P, Kiełczykowska M, Hordyjewska A, Szcześniak G, Musik I. Adipokine profile in patients with type 2 diabetes depends on degree of obesity. Medical Science Monitor. 2017;23:4995-5004. doi: https://doi.org/10.12659/msm.904318

Abudalo R, Alqudah A, Qnais E, Athamneh RY, Oqal M, Alnajjar R. Interplay of adiponectin and resistin in type 2 diabetes: Implications for insulin resistance and atherosclerosis. Pharmacia/Farmaciâ. 2024;71:1-8. doi: https://doi.org/10.3897/pharmacia.71.e114863

Cheung KKT, Luk AOY, So WY, Ma RCW, Kong APS, Chow FCC, et al. Testosterone level in men with type 2 diabetes mellitus and related metabolic effects: A review of current evidence. Journal of Diabetes Investigation. 2014;6:112-23. doi: https://doi.org/10.1111/jdi.12288

Laghari M, Murtaza S, Talpur Z, Memon KA, Tehzeen A, Hamid M. Serum testosterone level in type 2 diabetes mellitus. Journal of Pharmaceutical Research International. 2021;33:517-22. doi: https://doi.org/10.9734/jpri/2021/v33i44b32703

Gangwar SK, Verma SK, Modi S. Frequency and correlates of hypogonadism in adult males with type 2 diabetes mellitus. Indian Journal of Endocrinology and Metabolism. 2021;25:320-5. doi: https://doi.org/10.4103/ijem.ijem_239_21

Khalil SHA, Dandona P, Osman NA, Assaad RS, Zaitoon BTA, Almas AA, et al. Diabetes surpasses obesity as a risk factor for low serum testosterone level. Diabetol Metab Syndr. 2024 Jun 28;16(1):143. doi: https://doi.org/10.1186/s13098-024-01373-1

Wang X, Huang L, Jiang S, Cheng K, Wang D, Luo Q, et al. Testosterone attenuates pulmonary epithelial inflammation in male rats of COPD model through preventing NRF1-derived NF-κB signaling. Journal of Molecular Cell Biology. 2021;13:128-40. doi: https://doi.org/10.1093/jmcb/mjaa079

Traish A, Bolanos J, Nair S, Saad F, Morgentaler A. Do androgens modulate the pathophysiological pathways of inflammation? Appraising the contemporary evidence. Journal of Clinical Medicine. 2018;7:549. doi: https://doi.org/10.3390/jcm7120549

Grandys M, Majerczak J, Zapart-Bukowska J, Duda K, Kulpa JK, Zoladz JA. Lowered serum testos-terone concentration is associated with enhanced inflam-mation and worsened lipid profile in men. Frontiers in Endocrinology. 2021 Sep 9;12:735638. doi: https://doi.org/10.3389/fendo.2021.735638

Barnes PJ. Oxidative stress in chronic obstructive pulmonary disease. Antioxidants. 2022;11:965. doi: https://doi.org/10.3390/antiox11050965

Aschner Y, Downey GP. Transforming growth factor-β: master regulator of the respiratory system in health and disease. American Journal of Respiratory Cell and Molecular Biology. 2016;54:647-55. doi: https://doi.org/10.1165/rcmb.2015-0391tr

Kraik K, Tota M, Laska J, Łacwik J, Paździerz Ł, Sędek Ł, et al. The role of transforming growth factor-β (TGF-β) in asthma and chronic obstructive pulmonary disease (COPD). Cells. 2024;13:1271. doi: https://doi.org/10.3390/cells13151271

Chung J, Huda MN, Shin Y, Han S, Akter S, Kang I, et al. Correlation between oxidative stress and transforming growth factor-beta in cancers. International Journal of Molecular Sciences. 2021;22:13181. doi: https://doi.org/10.3390/ijms222413181

Cazzola M, Calzetta L, Rogliani P, Lauro D, Novelli L, Page CP, et al. High glucose enhances respon-siveness of human airways smooth muscle via the Rho/ROCK pathway. American Journal of Respiratory Cell and Molecular Biology. 2012;47:509-16. doi: https://doi.org/10.1165/rcmb.2011-0449oc

Dekkers BGJ, Saad SI, van Spelde LJ, Burgess JK. Basement membranes in obstructive pulmonary diseases. Matrix Biology Plus. 2021;12:100092. doi: https://doi.org/10.1016/j.mbplus.2021.100092

Cao Z, Liu Y, Wang Y, Leng P. Research progress on the role of PDGF/PDGFR in type 2 diabetes. Biomedicine & Pharmacotherapy. 2023;164:114983. doi: https://doi.org/10.1016/j.biopha.2023.114983

Kardas G, Daszyńska-Kardas A, Marynowski M, Brząkalska O, Kuna P, Panek M. Role of platelet-derived growth factor (PDGF) in asthma as an immunoregulatory factor mediating airway remodeling and possible pharmacological target. Frontiers in Pharmacology. 2020;11:47. doi: https://doi.org/10.3389/fphar.2020.00047

Mao QY, He SY, Hu QY, Lu Y, Niu YX, Li XY, et al. Advanced Glycation End Products (AGEs) Inhibit Macrophage Efferocytosis of Apoptotic β Cells through Binding to the Receptor for AGEs. J Immunol. 2022 Mar 1;208(5):1204-13. doi: https://doi.org/10.4049/jimmunol.2100695

Kapellos TS, Conlon TM, Yildirim AÖ, Leh-mann M. The impact of the immune system on lung injury and regeneration in COPD. Eur Respir J. 2023;62(4):2300589. doi: https://doi.org/10.1183/13993003.00589-2023

Pertseva NO, Chub DI. [Endothelial function factors as markers of progression of diabetic kidney disease]. Medychni perspektyvy. 2018;23(2, part 1):110. Ukrainian.

Poto R, Loffredo S, Palestra F, Marone G, Pa-tella V, Varricchi G. Angiogenesis, lymphangiogenesis, and inflammation in chronic obstructive pulmonary disease (COPD): few certainties and many outstanding questions. Cells. 2022;11:1720. doi: https://doi.org/10.3390/cells11101720

Sun X, Zhang H, Liu J, Wang G. Serum vascular endothelial growth factor level is elevated in patients with impaired glucose tolerance and type 2 diabetes mellitus. Journal of International Medical Research. 2019;47:5584-92. doi: https://doi.org/10.1177/0300060519872033

Kurniawan LB, Rika Andriany, Yuyun Wida-ningsih, Esa T, Uleng Bahrun, Adnan E, et al. Glycemic control as the main determinant factor of serum VEGF levels in type 2 diabetes mellitus patients. Romanian Journal of Internal Medicine. 2023;61:135-40. doi: https://doi.org/10.2478/rjim-2023-0009

Lourenço JD, Ito JT, Martins MA, Tibério IFLC, Lopes FDTQDS. Th17/Treg imbalance in chronic obstructive pulmonary disease: clinical and experimen-tal evidence. Front Immunol. 2021 Dec 9;12:804919. doi: https://doi.org/10.3389/fimmu.2021.804919

Ostedgaard LS, et al. Gel-forming mucins form distinct morphologic structures in airways. Proc Natl Acad Sci USA. 2017 Jun 27;114(26):6842-7. doi: https://doi.org/10.1073/pnas.1703228114

Li J, Ye Z. The Potential Role and Regulatory Me-chanisms of MUC5AC in Chronic Obstructive Pulmonary Disease. Molecules. 2020;25:4437. doi: https://doi.org/10.3390/molecules25194437

Song JS, Kang CM, Yoo MB, Kim SJ, Yoon HK, Kim YK, et al. Nitric oxide induces MUC5AC mucin in respiratory epithelial cells through PKC and ERK dependent pathways. Respir Res. 2007 Mar 29;8(1):28. doi: https://doi.org/10.1186/1465-9921-8-28

Wang C, Wang H, Dai L, Zhang J, Fang L, Liu L, et al. T-Helper 17 cell/regulatory T-Cell imbalance in COPD combined with T2DM patients. International Journal of Chronic Obstructive Pulmonary Disease. 2021;16:1425-35. doi: https://doi.org/10.2147/copd.s306406

Zhang S, Gang X, Yang S, Cui M, Sun L, Li Z, et al. The alterations in and the role of the Th17/Treg balance in metabolic diseases. Front Immunol. 2021 Jul 12;12:678355. doi: https://doi.org/10.3389/fimmu.2021.678355

Published

2025-09-29

How to Cite

1.
Sanina N, Sutyrin D, Turlyun T. Current understanding of the pathogenetic relationships between chronic obstructive pulmonary disease and type 2 diabetes mellitus: an integrative review. Med. perspekt. [Internet]. 2025Sep.29 [cited 2025Dec.5];30(3):81-9. Available from: https://journals.uran.ua/index.php/2307-0404/article/view/340743

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MEDICINE